The objective of the Center of Biomedical Research Excellence in the Molecular Basis of Human Disease (COBREMBHD) is to enhance the success of promising junior investigators at the University of Kentucky for competing for NIH grant support through the development of a research center focusing on understanding human disease at the molecular level. We will achieve this objective by: (1) assembling a group of established extramurally funded scientists who will serve as mentors for junior faculty serving as principal investigators on research projects. (2) providing these junior faculty with state-of-the-art training in concepts and techniques relevant to studying human disease with an emphasis on the application of structural biology to these projects, (3) establishing mentoring plans including milestones as the basis of the development program, (4) developing and supporting shared core facilities, (5) providing pilot grants for projects that will complement those of the junior faculty, (6) providing a seminar program stressing the latest advances in studying human diseases at the molecular level and techniques of structural biology and their application to biomedical research, (6) holding an annual retreat to evaluate and critique the progress of the junior faculty and (7) hiring promising new faculty to develop a critical mass of productive investigators in studying molecular aspects of human disease. Five tenure track Assistant Professors will serve as PIs on research projects that overlap in concepts and methodology. The junior investigators participating in the COBRE came from excellent postdoctoral experiences and are likely to benefit from the training program. Their projects apply one or more of the techniques of structural biology to studies related to human disease and have a high likelihood of developing into successful RO1 type research grants.